活体生物发光肺癌骨转移模型构建及其生物学特性

Establishment and biological characteristics of bioluminescent bone metastasis model of lung cancer in mice

在全世界范围内,肺癌一直是恶性肿瘤死亡的主要原因之一.肺癌容易复发和转移,其中骨转移是其常见的转移方式.将稳转Luciferase和GFP编码基因的A549细胞接种入胫骨内,第7天生物发光成像检测到胫骨腔内明显肿瘤生长信号.随着时间延长小鼠呈现明显的类似晚期癌症患者的恶液质现象,并伴随持续性疼痛和触觉疼痛.HE染色显示骨髓腔及骨小梁间被大量肿瘤细胞填充,骨髓腔和骨质结构破坏严重.骨肿瘤组织中肿瘤转移相关基因Mta1、Mta3高表达.上述结果表明,构建的骨转移模型具有人体肺癌骨转移相似的生物学特性及病理学表现,可用于开展肺癌骨转移相关机制研究、筛选开发抗肿瘤药物.此肺癌骨转移模型可以多时间点、动态地观测活体肿瘤病灶的生长情况,具有极高的检测灵敏度和非常高的医学应用价值.

Lung cancer has been one of the leading causes of cancer death worldwide,and is prone to recurrence and metastasis(bone metastasis,etc.).In this study,A549-Luc-GFP-Puro cells were screened to establish the bone metastasis model of lung cancer in vivo.After day 7 of injection,obvious tumor signal showed in the tibial cavity by vivo bioluminescent imaging.As the tumor signal increased,the mice lost weight and had persistent pain of leg with reduction of 50% pain threshold.HE staining indicated that the bone marrow cavity and trabecular were filled with highly proliferative tumor cells,and the bone structure was seriously damaged.Mta1 and Mta3,metastasis related genes,up-regulated in bone metastasis tumor.This bone metastasis model has similar biological characteristics and pathological manifestations with bone metastasis of human lung cancer.This model would be used to study the mechanism of bone metastasis of lung cancer and evaluate the efficacy of drugs,which is able to monitor the cancer growth dynamically and non-invasively at multiple time-points,and has highly medical value with high sensitivity and low experimental cost.